Comparing the Molecular Pharmacology of CGRP and Adrenomedullin

Abstract:

CGRP and adrenomedullin [AM] are peptides that have a number of physiological effects, including vasodilation,
through the activation of a shared GPCR, the family B calcitonin receptor-like receptor [CLR]. Specificity to each
ligand is conferred through the unusual association of CLR with a single transmembrane accessory protein. For CGRP this
is receptor activity-modifying protein 1 [RAMP1] and for AM acting at the AM1 receptor this is RAMP2. Receptor signalling
by two specific peptide ligands through a common GPCR provides researchers with vital and unique information
into similarities and differences of GPCR activation. Understanding the structure and function of these receptors will also
provide a platform for future drug design for a number of cardiovascular and metabolic diseases in which CGRP and AM
have been implicated. This review summarises the latest information and data concerning ligand binding, receptor activation
and structural studies for both the CGRP and AM receptors.

Abstract:CGRP and adrenomedullin [AM] are peptides that have a number of physiological effects, including vasodilation,
through the activation of a shared GPCR, the family B calcitonin receptor-like receptor [CLR]. Specificity to each
ligand is conferred through the unusual association of CLR with a single transmembrane accessory protein. For CGRP this
is receptor activity-modifying protein 1 [RAMP1] and for AM acting at the AM1 receptor this is RAMP2. Receptor signalling
by two specific peptide ligands through a common GPCR provides researchers with vital and unique information
into similarities and differences of GPCR activation. Understanding the structure and function of these receptors will also
provide a platform for future drug design for a number of cardiovascular and metabolic diseases in which CGRP and AM
have been implicated. This review summarises the latest information and data concerning ligand binding, receptor activation
and structural studies for both the CGRP and AM receptors.